3073 – HUMAN HAEMATOPOIETIC STEM AND PROGENITOR CELLS FORM KINSHIPS THAT ARE SIMILAR IN FATE AND SYNCHRONOUS IN DIVISION

Abstract

While the heterogeneity of human haematopoietic stem and progenitor cells has become apparent, linking this heterogeneity to functional properties at the single-cell level remains a challenge. Here, we have developed a combination of flow cytometry, live-cell imaging, and mathematical modelling to track the cell division properties and cell commitment in human haematopoietic stem and progenitor cells. We identified two key properties: synchronicity in division and similarity in fate among progenies of individual stem and progenitor cells. Each human stem and progenitor cell give rise to a cellular kinship that share a strong resemblance in fate and divide synchronously, suggesting an intrinsic cellular memory transmitted from mother to daughter cells. Interestingly, we observe that the time to divide shared by two sibling cells is not correlated with the division time of its mother cell. These behaviours are observed and shared across the entire lifespan, from cord blood to aged bone marrow cells. Moreover, we collected evidence that these behaviours are altered in haematological malignancies such as acute myeloid leukemia. Using a multi-agent mathematical model, we were able to recapitulate the cellular early commitment, where two sister cells descending from the same ancestor share a strong correlation in fate. In conclusion, we propose a model that describe the human haematopoiesis as a heterogeneous system formed by homogeneous cell families. While the heterogeneity of human haematopoietic stem and progenitor cells has become apparent, linking this heterogeneity to functional properties at the single-cell level remains a challenge. Here, we have developed a combination of flow cytometry, live-cell imaging, and mathematical modelling to track the cell division properties and cell commitment in human haematopoietic stem and progenitor cells. We identified two key properties: synchronicity in division and similarity in fate among progenies of individual stem and progenitor cells. Each human stem and progenitor cell give rise to a cellular kinship that share a strong resemblance in fate and divide synchronously, suggesting an intrinsic cellular memory transmitted from mother to daughter cells. Interestingly, we observe that the time to divide shared by two sibling cells is not correlated with the division time of its mother cell. These behaviours are observed and shared across the entire lifespan, from cord blood to aged bone marrow cells. Moreover, we collected evidence that these behaviours are altered in haematological malignancies such as acute myeloid leukemia. Using a multi-agent mathematical model, we were able to recapitulate the cellular early commitment, where two sister cells descending from the same ancestor share a strong correlation in fate. In conclusion, we propose a model that describe the human haematopoiesis as a heterogeneous system formed by homogeneous cell families.