A human lymphoma organoid model for evaluating and targeting the follicular lymphoma tumor immune microenvironment
Cell Stem Cell. 2024 Feb 20:S1934-5909(24)00042-0. doi: 10.1016/j.stem.2024.01.012. Online ahead of print.ABSTRACTHeterogeneity in the tumor microenvironment (TME) of follicular lymphomas (FLs) can affect clinical outcomes. Current immunotherapeutic strategies, including antibody- and cell-based therapies, variably overcome pro-tumorigenic mechanisms for sustained disease control. Modeling the intact FL TME, with its native, syngeneic tumor-infiltrating leukocytes, is a major challenge. Here, we describe an organoid culture method for cultivating patient-derived lymphoma organoids (PDLOs), which include cells from the nati...
Source: Cell Stem Cell - February 25, 2024 Category: Stem Cells Authors: Jenna M Kastenschmidt Joseph G Schroers-Martin Brian J Sworder Suhas Sureshchandra Michael S Khodadoust Chih Long Liu Mari Olsen David M Kurtz Maximilian Diehn Lisa E Wagar Ash A Alizadeh Source Type: research

An iron rheostat controls hematopoietic stem cell fate
Cell Stem Cell. 2024 Feb 19:S1934-5909(24)00041-9. doi: 10.1016/j.stem.2024.01.011. Online ahead of print.ABSTRACTMechanisms governing the maintenance of blood-producing hematopoietic stem and multipotent progenitor cells (HSPCs) are incompletely understood, particularly those regulating fate, ensuring long-term maintenance, and preventing aging-associated stem cell dysfunction. We uncovered a role for transitory free cytoplasmic iron as a rheostat for adult stem cell fate control. We found that HSPCs harbor comparatively small amounts of free iron and show the activation of a conserved molecular response to limited iron-p...
Source: Cell Stem Cell - February 25, 2024 Category: Stem Cells Authors: Yun-Ruei Kao Jiahao Chen Rajni Kumari Anita Ng Aliona Zintiridou Madhuri Tatiparthy Yuhong Ma Maria M Aivalioti Deeposree Moulik Sriram Sundaravel Daqian Sun Julie A Reisz Juliane Grimm Nuria Martinez-Lopez Stephanie Stransky Simone Sidoli Ulrich Steidl R Source Type: research

Region-specific cellular and molecular basis of liver regeneration after acute pericentral injury
Cell Stem Cell. 2024 Feb 21:S1934-5909(24)00043-2. doi: 10.1016/j.stem.2024.01.013. Online ahead of print.ABSTRACTLiver injuries often occur in a zonated manner. However, detailed regenerative responses to such zonal injuries at cellular and molecular levels remain largely elusive. By using a fate-mapping strain, Cyp2e1-DreER, to elucidate liver regeneration after acute pericentral injury, we found that pericentral regeneration is primarily compensated by the expansion of remaining pericentral hepatocytes, and secondarily by expansion of periportal hepatocytes. Employing single-cell RNA sequencing, spatial transcriptomics,...
Source: Cell Stem Cell - February 25, 2024 Category: Stem Cells Authors: Shuyong Wang Xuan Wang Yiran Shan Zuolong Tan Yuxin Su Yannan Cao Shuang Wang Jiahong Dong Jin Gu Yunfang Wang Source Type: research

A human lymphoma organoid model for evaluating and targeting the follicular lymphoma tumor immune microenvironment
Cell Stem Cell. 2024 Feb 20:S1934-5909(24)00042-0. doi: 10.1016/j.stem.2024.01.012. Online ahead of print.ABSTRACTHeterogeneity in the tumor microenvironment (TME) of follicular lymphomas (FLs) can affect clinical outcomes. Current immunotherapeutic strategies, including antibody- and cell-based therapies, variably overcome pro-tumorigenic mechanisms for sustained disease control. Modeling the intact FL TME, with its native, syngeneic tumor-infiltrating leukocytes, is a major challenge. Here, we describe an organoid culture method for cultivating patient-derived lymphoma organoids (PDLOs), which include cells from the nati...
Source: Cell Stem Cell - February 25, 2024 Category: Stem Cells Authors: Jenna M Kastenschmidt Joseph G Schroers-Martin Brian J Sworder Suhas Sureshchandra Michael S Khodadoust Chih Long Liu Mari Olsen David M Kurtz Maximilian Diehn Lisa E Wagar Ash A Alizadeh Source Type: research

An iron rheostat controls hematopoietic stem cell fate
Cell Stem Cell. 2024 Feb 19:S1934-5909(24)00041-9. doi: 10.1016/j.stem.2024.01.011. Online ahead of print.ABSTRACTMechanisms governing the maintenance of blood-producing hematopoietic stem and multipotent progenitor cells (HSPCs) are incompletely understood, particularly those regulating fate, ensuring long-term maintenance, and preventing aging-associated stem cell dysfunction. We uncovered a role for transitory free cytoplasmic iron as a rheostat for adult stem cell fate control. We found that HSPCs harbor comparatively small amounts of free iron and show the activation of a conserved molecular response to limited iron-p...
Source: Cell Stem Cell - February 25, 2024 Category: Stem Cells Authors: Yun-Ruei Kao Jiahao Chen Rajni Kumari Anita Ng Aliona Zintiridou Madhuri Tatiparthy Yuhong Ma Maria M Aivalioti Deeposree Moulik Sriram Sundaravel Daqian Sun Julie A Reisz Juliane Grimm Nuria Martinez-Lopez Stephanie Stransky Simone Sidoli Ulrich Steidl R Source Type: research

Region-specific cellular and molecular basis of liver regeneration after acute pericentral injury
Cell Stem Cell. 2024 Feb 21:S1934-5909(24)00043-2. doi: 10.1016/j.stem.2024.01.013. Online ahead of print.ABSTRACTLiver injuries often occur in a zonated manner. However, detailed regenerative responses to such zonal injuries at cellular and molecular levels remain largely elusive. By using a fate-mapping strain, Cyp2e1-DreER, to elucidate liver regeneration after acute pericentral injury, we found that pericentral regeneration is primarily compensated by the expansion of remaining pericentral hepatocytes, and secondarily by expansion of periportal hepatocytes. Employing single-cell RNA sequencing, spatial transcriptomics,...
Source: Cell Stem Cell - February 25, 2024 Category: Stem Cells Authors: Shuyong Wang Xuan Wang Yiran Shan Zuolong Tan Yuxin Su Yannan Cao Shuang Wang Jiahong Dong Jin Gu Yunfang Wang Source Type: research

A human lymphoma organoid model for evaluating and targeting the follicular lymphoma tumor immune microenvironment
Cell Stem Cell. 2024 Feb 20:S1934-5909(24)00042-0. doi: 10.1016/j.stem.2024.01.012. Online ahead of print.ABSTRACTHeterogeneity in the tumor microenvironment (TME) of follicular lymphomas (FLs) can affect clinical outcomes. Current immunotherapeutic strategies, including antibody- and cell-based therapies, variably overcome pro-tumorigenic mechanisms for sustained disease control. Modeling the intact FL TME, with its native, syngeneic tumor-infiltrating leukocytes, is a major challenge. Here, we describe an organoid culture method for cultivating patient-derived lymphoma organoids (PDLOs), which include cells from the nati...
Source: Cell Stem Cell - February 25, 2024 Category: Stem Cells Authors: Jenna M Kastenschmidt Joseph G Schroers-Martin Brian J Sworder Suhas Sureshchandra Michael S Khodadoust Chih Long Liu Mari Olsen David M Kurtz Maximilian Diehn Lisa E Wagar Ash A Alizadeh Source Type: research

An iron rheostat controls hematopoietic stem cell fate
Cell Stem Cell. 2024 Feb 19:S1934-5909(24)00041-9. doi: 10.1016/j.stem.2024.01.011. Online ahead of print.ABSTRACTMechanisms governing the maintenance of blood-producing hematopoietic stem and multipotent progenitor cells (HSPCs) are incompletely understood, particularly those regulating fate, ensuring long-term maintenance, and preventing aging-associated stem cell dysfunction. We uncovered a role for transitory free cytoplasmic iron as a rheostat for adult stem cell fate control. We found that HSPCs harbor comparatively small amounts of free iron and show the activation of a conserved molecular response to limited iron-p...
Source: Cell Stem Cell - February 25, 2024 Category: Stem Cells Authors: Yun-Ruei Kao Jiahao Chen Rajni Kumari Anita Ng Aliona Zintiridou Madhuri Tatiparthy Yuhong Ma Maria M Aivalioti Deeposree Moulik Sriram Sundaravel Daqian Sun Julie A Reisz Juliane Grimm Nuria Martinez-Lopez Stephanie Stransky Simone Sidoli Ulrich Steidl R Source Type: research

Region-specific cellular and molecular basis of liver regeneration after acute pericentral injury
Cell Stem Cell. 2024 Feb 21:S1934-5909(24)00043-2. doi: 10.1016/j.stem.2024.01.013. Online ahead of print.ABSTRACTLiver injuries often occur in a zonated manner. However, detailed regenerative responses to such zonal injuries at cellular and molecular levels remain largely elusive. By using a fate-mapping strain, Cyp2e1-DreER, to elucidate liver regeneration after acute pericentral injury, we found that pericentral regeneration is primarily compensated by the expansion of remaining pericentral hepatocytes, and secondarily by expansion of periportal hepatocytes. Employing single-cell RNA sequencing, spatial transcriptomics,...
Source: Cell Stem Cell - February 25, 2024 Category: Stem Cells Authors: Shuyong Wang Xuan Wang Yiran Shan Zuolong Tan Yuxin Su Yannan Cao Shuang Wang Jiahong Dong Jin Gu Yunfang Wang Source Type: research

A human lymphoma organoid model for evaluating and targeting the follicular lymphoma tumor immune microenvironment
Cell Stem Cell. 2024 Feb 20:S1934-5909(24)00042-0. doi: 10.1016/j.stem.2024.01.012. Online ahead of print.ABSTRACTHeterogeneity in the tumor microenvironment (TME) of follicular lymphomas (FLs) can affect clinical outcomes. Current immunotherapeutic strategies, including antibody- and cell-based therapies, variably overcome pro-tumorigenic mechanisms for sustained disease control. Modeling the intact FL TME, with its native, syngeneic tumor-infiltrating leukocytes, is a major challenge. Here, we describe an organoid culture method for cultivating patient-derived lymphoma organoids (PDLOs), which include cells from the nati...
Source: Cell Stem Cell - February 25, 2024 Category: Stem Cells Authors: Jenna M Kastenschmidt Joseph G Schroers-Martin Brian J Sworder Suhas Sureshchandra Michael S Khodadoust Chih Long Liu Mari Olsen David M Kurtz Maximilian Diehn Lisa E Wagar Ash A Alizadeh Source Type: research

Thalamocortical organoids enable in  vitro modeling of 22q11.2 microdeletion associated with neuropsychiatric disorders
Cell Stem Cell. 2024 Feb 13:S1934-5909(24)00040-7. doi: 10.1016/j.stem.2024.01.010. Online ahead of print.ABSTRACTThalamic dysfunction has been implicated in multiple psychiatric disorders. We sought to study the mechanisms by which abnormalities emerge in the context of the 22q11.2 microdeletion, which confers significant genetic risk for psychiatric disorders. We investigated early stages of human thalamus development using human pluripotent stem cell-derived organoids and show that the 22q11.2 microdeletion underlies widespread transcriptional dysregulation associated with psychiatric disorders in thalamic neurons and g...
Source: Cell Stem Cell - February 21, 2024 Category: Stem Cells Authors: David Shin Chang N Kim Jayden Ross Kelsey M Hennick Sih-Rong Wu Neha Paranjape Rachel Leonard Jerrick C Wang Matthew G Keefe Bryan J Pavlovic Kevin C Donohue Clara Moreau Emilie M Wigdor H Hanh Larson Denise E Allen Cathryn R Cadwell Aparna Bhaduri Galina Source Type: research

Hallmarks of totipotent and pluripotent stem cell states
Cell Stem Cell. 2024 Feb 13:S1934-5909(24)00039-0. doi: 10.1016/j.stem.2024.01.009. Online ahead of print.ABSTRACTThough totipotency and pluripotency are transient during early embryogenesis, they establish the foundation for the development of all mammals. Studying these in vivo has been challenging due to limited access and ethical constraints, particularly in humans. Recent progress has led to diverse culture adaptations of epiblast cells in vitro in the form of totipotent and pluripotent stem cells, which not only deepen our understanding of embryonic development but also serve as invaluable resources for animal reprod...
Source: Cell Stem Cell - February 21, 2024 Category: Stem Cells Authors: Peng Du Jun Wu Source Type: research

Thalamocortical organoids enable in  vitro modeling of 22q11.2 microdeletion associated with neuropsychiatric disorders
Cell Stem Cell. 2024 Feb 13:S1934-5909(24)00040-7. doi: 10.1016/j.stem.2024.01.010. Online ahead of print.ABSTRACTThalamic dysfunction has been implicated in multiple psychiatric disorders. We sought to study the mechanisms by which abnormalities emerge in the context of the 22q11.2 microdeletion, which confers significant genetic risk for psychiatric disorders. We investigated early stages of human thalamus development using human pluripotent stem cell-derived organoids and show that the 22q11.2 microdeletion underlies widespread transcriptional dysregulation associated with psychiatric disorders in thalamic neurons and g...
Source: Cell Stem Cell - February 21, 2024 Category: Stem Cells Authors: David Shin Chang N Kim Jayden Ross Kelsey M Hennick Sih-Rong Wu Neha Paranjape Rachel Leonard Jerrick C Wang Matthew G Keefe Bryan J Pavlovic Kevin C Donohue Clara Moreau Emilie M Wigdor H Hanh Larson Denise E Allen Cathryn R Cadwell Aparna Bhaduri Galina Source Type: research

Hallmarks of totipotent and pluripotent stem cell states
Cell Stem Cell. 2024 Feb 13:S1934-5909(24)00039-0. doi: 10.1016/j.stem.2024.01.009. Online ahead of print.ABSTRACTThough totipotency and pluripotency are transient during early embryogenesis, they establish the foundation for the development of all mammals. Studying these in vivo has been challenging due to limited access and ethical constraints, particularly in humans. Recent progress has led to diverse culture adaptations of epiblast cells in vitro in the form of totipotent and pluripotent stem cells, which not only deepen our understanding of embryonic development but also serve as invaluable resources for animal reprod...
Source: Cell Stem Cell - February 21, 2024 Category: Stem Cells Authors: Peng Du Jun Wu Source Type: research

Thalamocortical organoids enable in  vitro modeling of 22q11.2 microdeletion associated with neuropsychiatric disorders
Cell Stem Cell. 2024 Feb 13:S1934-5909(24)00040-7. doi: 10.1016/j.stem.2024.01.010. Online ahead of print.ABSTRACTThalamic dysfunction has been implicated in multiple psychiatric disorders. We sought to study the mechanisms by which abnormalities emerge in the context of the 22q11.2 microdeletion, which confers significant genetic risk for psychiatric disorders. We investigated early stages of human thalamus development using human pluripotent stem cell-derived organoids and show that the 22q11.2 microdeletion underlies widespread transcriptional dysregulation associated with psychiatric disorders in thalamic neurons and g...
Source: Cell Stem Cell - February 21, 2024 Category: Stem Cells Authors: David Shin Chang N Kim Jayden Ross Kelsey M Hennick Sih-Rong Wu Neha Paranjape Rachel Leonard Jerrick C Wang Matthew G Keefe Bryan J Pavlovic Kevin C Donohue Clara Moreau Emilie M Wigdor H Hanh Larson Denise E Allen Cathryn R Cadwell Aparna Bhaduri Galina Source Type: research